PROJECT SUMMARY Novel inhibitors of BK polyomavirus (BKPyV) are urgently needed to prevent the occurrence of virus-induced nephropathy, allograft failure and hemorrhagic cystitis following transplantation. The objective of this Phase I SBIR feasibility study is to identify drug-like compounds that specifically inhibit BKPyV replication. During the course of this Phase I funding period, we will execute a hit finding campaign with a library of 100,000 compounds with optimal drug-like properties. Quality hits that emerge from the assay will be subjected to follow-on testing that will investigate the potency, selectivity, and mechanism of action. The most interesting of these compounds will be subjected to medicinal chemistry driven hit-to-lead efforts to explore structure-activity relationships (SAR). The overall goal of this project is to discover one or more novel lead series, which is defined as a chemotype inhibitor that demonstrates tractable SAR, potent antiviral activity against the available BKPyV strains and minimal cytotoxicity. Success in these endeavors will trigger the submission of a Phase II application that will advance the program from Early Lead Optimization through to Candidate Selection.